Pharmacological agents which possess a chemosensitizing activity (i.e. the ability to modulate the multidrug resistance phenotype) can equally enhance ligand-toxin conjugate cytotoxicity. By confronting results obtained in both fields of research it appears that quite a number of agents, which are structurally unrelated, possess this bilateral effect. We have therefore attempted to provide a brief review of the literature and to discuss a hypothesis by which a common mechanism such as modifications in intracellular vesicle sorting and/or lipid metabolism may be implicated. We believe that these observations may provide clues for future research.